The goal of this investigation is to evaluate biological factors in the depression of Parkinson Disease (PD) as a model of depression in the elderly. The prevalence and severity of depression will be determined and the associated intellectual changes will be documented. The relationship between the severity of PD, independence in daily activities, and depression will be analyzed. Metabolites of serotonin and norepinephrine in cerebrospinal fluid and urine will be studied. The functional integrity of the hypothalamus will be examined by provocative methods of stimulation and inhibition of anterior pituitary hormones, and by examining responses to thermal stress. The long term objective of this study is to determine the role of the biogenic amines, serotonin and norepinephrine, in depression in PD, and to determine the relationship of degenerative changes within the hypothalamus in PD to depression. A longitudinal, prospective investigation is planned over three years. Hospitalization will be required in the General Clinical Research Center for purposes of withdrawing medication during the biochemical studies. The endeavor will cross several disciplines including Psychiatry, Neuropsychology, Neurochemistry, Neuroendocrinology and Neurology. Depression and dementia constitute two major clinical features of PD that are poorly understood. These two disorders are also major health problems for the aged, and PD may serve as a model disease for the study of depression. Metabolic studies of primary depressive disorders implicate disturbances within the monoamine and hypothalamic-peptide systems, but are lacking in pathological verification. On the other hand, pathological changes in hypothalamus and loss of monoamines in PD are recognized, however, clinicopathological correlation is lacking. Should a relationship exist, it would broaden our understanding of the pathophysiological mechanisms underlying depression not only in PD but aging as well.